Association of common gene variants in the WNT/beta-catenin pathway with colon cancer recurrence
Por:
Paez, D, Gerger, A, Zhang, W, Yang, D, Labonte, MJ, Benhanim, L, Kahn, M, Lenz, F, Lenz, C, Ning, Y, Wakatsuki, T, Loupakis, F, Lenz, HJ
Publicada:
1 abr 2014
Resumen:
Wnt/beta-catenin signaling has a central role in the development and progression of most colon cancers (CCs). Germline variants in Wnt/beta-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/beta-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II CC. A total of 234 patients treated with 5-fluorouracil-based chemotherapy were included in this study. Whole-blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4, NOTCH2 and GLI1 genes by PCR-based restriction fragment-length polymorphism or direct DNA sequencing. Polymorphisms with statistical significance were validated in an independent study cohort. The minor allele of WNT5B rs2010851 T > G was significantly associated with a shorter TTR (10.7 vs 4.9 years; hazard ratio: 2.48; 95% CI, 0.96-6.38; P=0.04) in high-risk stage II CC patients. This result remained significant in multivariate Cox's regression analysis. This study shows that the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for CC patients after 5-fluorouracil-based adjuvant therapy.
Filiaciones:
Paez, D:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona, Spain
Gerger, A:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Med Univ Graz, Div Clin Oncol, Dept Internal Med, Res Unit Genet Epidemiol & Pharmacogenet, Graz, Austria
Zhang, W:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Yang, D:
Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA
Labonte, MJ:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Azusa Pacific Univ, Dept Biol & Chem, Azusa, CA USA
Benhanim, L:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Kahn, M:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Lenz, F:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Lenz, C:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Ning, Y:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Wakatsuki, T:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Loupakis, F:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Lenz, HJ:
Univ So Calif, Keck Sch Med, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA
Univ So Calif, Keck Sch Med, Ctr Mol Pathways & Drug Discovery, Los Angeles, CA 90033 USA
Bronze
|